In silico prediction of dermal absorption of pesticides – an evaluation of selected models against results from in vitro testing

Abstract

Current guidance for the estimation of dermal absorption (DA) of pesticides recommends the use of default values, read-across of information between formulations and in vitro testing. While QSARs exist to estimate percutaneous absorption, their use is currently not encouraged. Therefore, the potential of publicly available models for DA estimation was investigated based on data from 564 human in vitro DA experiments on pesticides. The classic Potts Guy model, the correction of Cleek Bunge for highly lipophilic chemicals, the mechanistic model of Mitragotri, and the COSMOS model were used to estimate the permeability coefficient k p. Different approaches were explored to calculate the percentage of external dose absorbed. IH SkinPerm was examined as stand-alone model. The models generally failed to accurately predict experimental values. For 30-40% of the predictions, there was overestimation by one order of magnitude. Three models underpredicted >10% of the cases, the remaining models <5%. DA of hydrophilic substances was typically underpredicted. Overprediction was more prominent for solid preparations and suspensions. The molecular weight, irritation potential and skin thickness did not correlate with the models' predictivity. Of the models investigated, IH SkinPerm performed best with 38% of the predictions within one order of magnitude and 2% underpredicted cases.

In Vitro Human Dermal Absorption Studies on Pesticides in Complex Mixtures: Investigation of Guidance Criteria and Possible Impact Parameters

“…In particular, pesticide products are formulated to ensure or increase the efficacy of the active substance. Eleftheriadou et al [ 18 ] investigated the potential for the prediction of the dermal absorption of substances in complex mixtures of plant protection products using several published models developed for single substances in simple solutions. The models generally failed to accurately predict experimental values.…”

Integrating mathematical approaches (IMAS): Novel methodology for predicting dermal absorption rates of chemicals under finite dose conditions

“…Although convenient, precision may be compromised due to the discrete values in Kroes' methodology. Additionally, Buist et al (2010) developed a mathematical model to predict DA using Kp but overlooked the limitation of target chemical exposure time due to vehicle evaporation, leading to overestimation (Buist et al, 2010;Eleftheriadou et al, 2019). To address this issue, we developed a mathematical model considering vehicle evaporation and Kp values, which were obtained from in vitro transdermal absorption studies under infinite dose conditions; the model exhibited high prediction accuracy (correlation coefficient > 0.9) with a limited number (seven) of chemical cases (Kunita et al, 2022).…”

Secondary Data Analysis on Pesticide-Gene-Disease Relations

“…Since 2008, Brazil is one of the largest pesticide consumers globally, consuming one million tons from 2011 to now. This consumption level makes Brazil responsible for 86% of all pesticide consumption in Latin America (Eleftheriadou et al, 2019). Thus, more effective control of pesticide use is necessary and should be based on scientific data.…”